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. 2016 Jul 8;82(4):903–922. doi: 10.1111/bcp.13018

Table 6.

Schematic summary of results of randomized controlled trials investigating hyperalgesia induced by thermode burn, according to type of challenge

Drug class Drug (administration form/dose) Challenge type Challenge/outcome Overall effect
Effective No effect
Opioids Morphine (IV injection/2 mg) 74A; (IV infusion/0.14 mg kg–1, 0.28 mg kg–1) 117A†; (IV infusion/0.1 mg kg–1) 69A; (IV infusion/0.15 mg kg–1) 70A; (IV infusion/0.205 mg kg–1 in 80 min) 71A; (Oral/30 mg) 72A; (subcutaneous injection in burn/2 mg) 74B; (subcutaneous injection in burn/2 mg) 118 Morphine (IV Infusion / 0.1 mg kg–1) & Ketamine (IV Infusion / 0.405 mg kg–1) 69B;
Morphine (Oral / 30 mg) & Dextrometorphan (Oral / 30 mg) 72B
Fentanyl (Local injection / 10 μg) 75
Alfentanil (IV infusion / 73 μg kg–1) 117B† 		T Heat/PDT 75, *, 118 74A, 74B, 71A, 70A
Cold/PDT 70A
Heat/rating 74A, 74B, 75
M Pin prick/area 71A, 72B, 117B‡ 74A, 74B, 117A, 69A, 69B, 70A, 72A
Pin prick/pain rating 69B 74A, 74B, 69A, 75
Pin prick/PDT 69B, 117A§, 117B‡ 74A, 74B, 69A, 71A
Stroking/area 71A 72A, 72B, 70A
Impact stimulus/PDT 118
S‐I Spontaneous pain 74A, 74B
Opioid antagonists Naloxone (IV bolus/0.4 mg) 87 T Heat/PDT 87
Heat/rating 87
M Pin prick/area 87
Stroking/area 87
Anaesthetics Lidocaine (IV infusion/317.5 mg) 76 EMLA (topical cream/2 g 2.5% Lignocaine and 2.5% Procaine) 77 T Heat/PDT 76, 77
Heat/pain rating
M Pin prick/area 76, 77
Pin prick/PDT 76, 77
S‐I Flare/area 76
Flare/intensity 77
NSAIDs Ibuprofen (oral/500 mg) 81; (oral/600 mg) 82A; (topical cream/3 g) 82B Ketorolac (local injection/0.3 mg) 78; (topical gel/0.075 g) 80; (IV injection/60 mg) 119;
Piroxicam (topical gel/5 mg) 79 		T Heat/PDT 82A, 82B, 79, 80
Heat/rating 78
Heat/PTT 82A, 82B, 79, 80
M Pin prick/area 119 81, 82A, 82B, 79, 80
Pin prick/PDT 79, 80
Stroking/area 81
Stroking/pain rating 81
S‐I Flare/intensity 79, 80
Spontaneous pain 81
Calcium channel α2‐δ ligands Gabapentin (oral/1200 mg) 45, 85 T Heat/PDT 85
M Pin prick/area 45 85
Pin prick/pain rating 85
Pin prick/PDT 85
Stroking/area 85
S‐I Spontaneous pain 85
NMDA receptor antagonists Ketamine (IV infusion/0.49 mg kg–1 in 150 min) 65A; (IV infusion/0.98 mg kg–1 in 150 min) 65B; (IV infusion/0.405 mg kg–1 in 45 min) 69B; (IV infusion/0.15 mg kg–1) 70B; (IV Infusion/0.39 mg kg–1 in 80 min) 71B; (oral/0.5 mg kg–1, 1.0 mg kg–1) 73; (IV infusion/0.3 mg kg–1 in 15 min, then 0.3 mg kg–1 h–1 for 15 min) 67A; (systemic subcutaneous injection/15 mg) 68A; (local subcutaneous injection/7.5 mg) 68B; Naloxone (IV infusion / 0.8 mg kg–1 in 15 minutes) & Ketamine (IV Infusion / 0.375 mg kg–1 per 30 minutes) 67B
Dextrometorphan (Oral / 60 mg, 120 mg) 66; (IV infusion / 0.5 mg kg–1) 55; (Oral / 30 mg) 72 		T Heat/PDT 65B 65A, 73, 71B, 70B, 68A, 68B, 67A, 67B, 66
Heat/rating 68A, 68B
Cold/PDT 70B
M Pin prick/area 65B, 70B††, 71B, 67A, 67B**, 66, ‡‡, 55, §§, 69B¶¶ 65A, 73, 68A, 68B, 72
Pin prick/PDT 71B***, 68B†††, 69B 68A
Pin prick/pain rating 68A, 68B, 69B
Stroking/area 65A***, 65B, 70B†††, 71B¶¶¶, 67A, 67B** 66, 72, 73, 68A, 68B
S‐I Spontaneous pain 65B, 68B 65A, 73, 68A, 66
Glutamate receptor antagonists Riluzole (oral/300 mg) 86 T Heat/PDT 86
Heat/rating 86
M Pin prick/area 86
Pin prick/PDT 86
Pin prick/pain rating 86
S‐I Spontaneous pain 86
Corticosteroids Clobetasol propionate (topical cream/0.05 g) 83; Dexamethasone (IV infusion/8 mg) 84;
Methylprednisolone (IV injection/125 mg) 119 		T Heat/PDT 83, 84
Heat/PTT 83
Heat/pain rating 84
M Pin prick/area 119 83, 84
Pin prick/PDT 83, 84
Pin prick/pain rating 84
S‐I Flare/intensity 83, 84
Spontaneous pain 84
Hormones Melatonin (IV infusion/100 mg****) 120 T Heat/PDT 120
M Pin prick/area 120
Pin prick/PDT 120
Impact stimulus/PDT 120
Impact stimulus/PTT 120
S‐I Flare/intensity 120
Spontaneous pain 120
Antiarrhythmic agents Adenosine (IV infusion/7.2 mg kg–1) 15 T Heat/PDT 15
Heat/rating 15
M Pin prick/PDT 15
Pin prick/area 15
Pin prick/pain rating 15

IV, intravenous; EMLA, eutectic mixture of local anaesthetics; M, mechanical; NMDA, N‐methyl‐D‐aspartate; NSAID, nonsteroidal anti‐inflammatory drug; PDT, pain detection threshold; PTT, pain tolerance threshold; S‐I, stimulus‐independent; T, thermal.

*

Concomitant treatment with naloxone (80 μg) reversed this statistically significant reduction in pain score.

†

Compared with saline or active placebo: midazolam (2 mg kg–1 min–1).

‡

Only significant effect when measured during infusion 85 min postburn, and not 80 min post‐infusion 205 min postburn.

§

Significant difference only seen at high dose (0.28 mg kg–1) at late phase (80 min postdosing), not in earlier measurements.

Only significant difference up to 45 min postdosing.

**

Only effect at late phase (135 min postburn).

††

Only short‐term effect: no significant difference from 15 min postdosing onwards.

‡‡

Only at specific time point (180 min postburn, not before or after) at high dose (120 mg).

§§

Significant difference from 90 min to 180 min postdosing, not earlier.

¶¶

Only significant effect at 45 min postdosing, not at 75 min postdosing.

***

Only short‐term effect during infusion; no significant difference at 80 min or 120 min postdosing.

†††

Only significant effect at 0 min postburn; no significant difference at 60 min or 120 min postburn.

‡‡‡

Only significant effect at 100 min postdosing, not at 60 min or 160 min postdosing.

§§§

Only short‐term effect: no significant difference from 15 min postdosing onwards.

¶¶¶

Only short‐term effect during infusion; no significant difference at 80 min or 120 min postdosing.

****

Administration of melatonin 10 mg IV infusion demonstrated equal lack of analgesic effect on all parameters. Numbers between brackets signify references. Studies that investigated more than one type of pharmacological intervention are denoted with a letter (A,B,C).